This proposal is for continued support for the multi-disciplinary Diabetes and Obesity Center at the University of Louisville. The central focus of the Center is to enable, promote and support research on the cardiovascular causes and consequences of diabetes and obesity. The second major aim of the program is to continue to provide mentoring and guidance to junior investigators in the Center. Specific objectives of the program are to: (1) Enhance and expand a thematic multi-disciplinary research center focused on diabetes and obesity; (2) Foster the research careers of junior investigators, leading to their development as independent principal investigators; (3) Develop a nationally-competitive program that will attract the best clinical and post-doctoral fellows, graduate students, and faculty; (4) Expand and bridge on-going research within the Center and further integrate current expertise into a thematically coherent program; (5) Promote collaborative interactions to build additional complementary research projects, both individual and multi-investigator; (6) Build upon existing research capabilities and core facilities to provide state-of-the-art infrastructure support; (7) Develop basic and clinical understanding of the molecular mechanisms of diabetes and obesity and how they contribute to the burden of cardiovascular disease; (8) Discover new and effective means for preventing and treating diabetes and obesity; and (9) Develop and implement a plan for the transition from COBRE support to independent funding. The five related projects of the junior investigators will: (1) Examine the effects of dietary carnosine on diabetes and obesity; (2) Assess the impact of particulate air pollution on insulin resistance; (3) Elucidate the role of eNOS in obesity; (4) Assess stem cell dysfunction in diabetes; and (5) Develop biomarkers for detecting atherothrombotic events in patients with type 2 diabetes. These investigations will be supported by state-of-the-art core facilities in flow cytometry, pathology and bioanalytical chemistry, imaging and physiology and animal model development and phenotyping. Continued support to the Center will strengthen the infrastructure of biomedical research at the University of Louisville and will positively impact the field of diabete and obesity research worldwide.